Abstract
Days via catheters implanted in the intrathecal space. Clonidine was administered at a dose of 1.63 μg or 16.3 μg, and guanfacine at 16.3 or 75 μg. After perfusion with a buffered 3% glutaraldehyde solution, the spinal cords and nerve roots were taken for neuropathological analysis using light and electron microscopy. Compared to animals injected with 0.9% saline, clonidine and guanfacine gave rise to no detectable neurotoxic changes in the doses employed. An additional group of rats had intrathecal injections of a substance P-antagonist (D-Arg1, D-Trp7,9, Leu11)-substance P (spantide) with known neurotoxic effect as a test of the histotechnical methods used. Degenerative lesions, with a preference for the ventral horns, were consistently present in the grey matter of the cord in these animals. We conclude that the absence of detectable changes in rats given clonidine and guanfacine is probably a real expression of the low degree of toxicity for these compounds on rat spinal cord and nerve roots and not an artifact of the sensitivity of the histotechniques applied. The doses of clonidine administered were considerably greater than those reported to produce clinical greater than those reported to produce clinical analgesia. Address correspondence to Dr. Gordh, Department of Anaesthesiology, University Hospital, S-751 85 Uppsala, Sweden. This work was supported by grants from the Bank of Sweden Trecentenary Foundation (81/120, A. Tamsen) and from the Swedish Medical Research Council, project 12X-03020. We gratefully acknowledge the help of Ewa Arweström, Madeleine Jarild, Gunilla Tibbling, and Christer Tengvar for advice and excellent technical assistance. We would also like to thank Boehringer Ingelheim and Sandoz for the supply of clonidine and guanfacine, respectively. Accepted for publication July 21, 1986. © 1986 International Anesthesia Research Society...